Neuroimmune drivers of tendon pain
Tendon pain significantly impairs mobility and quality of life, yet the biological mechanisms that regulate healing remain poorly understood. The local tissue environment facilitates dynamic communication between sensory nerves, resident tendon cells, and immune populations. These interactions influence both cell behavior and the overall healing response. However, the pathways that connect these cellular interactions to pain and healing remain underexplored and continue to limit the development of effective targeted therapies. This work aims to investigate how neuroimmune cues shape tendon healing and pain by integrating controlled in vitro tendon systems with pre-linical models of tendon injury and disease, validated using human tendon tissue. Together, these approaches bridge bench-to-bedside to uncover the mechanisms underlying tendon pain.
Exploring Biomimetic Tendon Models to Elucidate Underlying Pathological Mechanisms
Tendons rely on exercise to maintain tissue health, but repetitive overloading can cause tendinopathy, reduce tissue quality, and perturb homeostatic cellular processes. Current treatments focus on load management and often fail to address underlying cellular dysfunction, leaving the link between tendon cells and biomechanical cues unclear. In the Taylor Lab, we strain biomimetic scaffolds seeded with tendon-derived cells to create biomechanical in vitro models of healthy and diseased tendons to elucidate tissue maintenance responses. We also employ inclined treadmill running to induce Achilles tendinopathy in rats, providing in vivo models to assess pathological development. Across both approaches, we integrate age as a critical factor to understand its role in tendon health and disease.
Biomimetic Matrices
The idea behind biomimetic matrices, such as pre-vascularized scaffolds, is to mimic the structural and biological processes during musculoskeletal tissue development and design functional biomimetic structures such as decellularized pre-vascularized osteonic structures which promote stable blood vessel formation in vivo throughout bone healing.
Subcellular Components
Tendon fibrosis results in reduced functionality and increased risk of re-injury, yet the cellular and molecular mechanisms driving tendon healing remain incompletely understood. Healing is regulated by both extrinsic and intrinsic cell activities, often leading to fibrotic tissue with poor mechanical integrity. Extracellular vesicles (EVs), which mediate cell-to-cell communication and transport bioactive molecules, have emerged as key players in tissue repair. However, the specific role of EVs in modulating tendon fibrosis remains largely unexplored. This work aims to investigate how different microenvironments influence EV phenotype and function in healthy and diseased in vitro tendon models.
